In general, cellular processes are a combination of many complex sets of interactions that include gene transcription, mRNA translation, protein-RNA interactions, protein-DNA interactions, protein-protein interactions, and protein modifications such as phosphorylation. As biology moves forward with a “systems biology” approach, so must imaging of molecular/cellular events in living subjects, to lead to a “systems imaging” approach. It will be important to characterize more complex interactions that occur in living subjects by developing approaches that can monitor intracellular communication pathways including protein phosphorylation. Protein phosphorylation is at the heart of signal transduction, developmental biology, cell assembly, cellular metabolism, and a whole array of other biological processes. In addition, many cellular protein-protein interactions are specifically controlled by phosphorylation and de-phosphorylation of proteins at specific amino acids in sequence-specific regions. Therefore, methods are needed that would allow imaging of complex interactions in the context of intact cells anywhere within a living subject.